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Publication : Thyrotropin aggravates atherosclerosis by promoting macrophage inflammation in plaques.

First Author  Yang C Year  2019
Journal  J Exp Med Volume  216
Issue  5 Pages  1182-1198
PubMed ID  30940720 Mgi Jnum  J:275221
Mgi Id  MGI:6305944 Doi  10.1084/jem.20181473
Citation  Yang C, et al. (2019) Thyrotropin aggravates atherosclerosis by promoting macrophage inflammation in plaques. J Exp Med 216(5):1182-1198
abstractText  Subclinical hypothyroidism is associated with cardiovascular diseases, yet the underlying mechanism remains largely unknown. Herein, in a common population (n = 1,103), TSH level was found to be independently correlated with both carotid plaque prevalence and intima-media thickness. Consistently, TSH receptor ablation in ApoE (-/-) mice attenuated atherogenesis, accompanied by decreased vascular inflammation and macrophage burden in atherosclerotic plaques. These results were also observed in myeloid-specific Tshr-deficient ApoE (-/-) mice, which indicated macrophages to be a critical target of the proinflammatory and atherogenic effects of TSH. In vitro experiments further revealed that TSH activated MAPKs (ERK1/2, p38alpha, and JNK) and IkappaB/p65 pathways in macrophages and increased inflammatory cytokine production and their recruitment of monocytes. Thus, the present study has elucidated the new mechanisms by which TSH, as an independent risk factor of atherosclerosis, aggravates vascular inflammation and contributes to atherogenesis.
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